Upregulation of the inducible nitric oxide synthase in rat hippocampus in a model of Alzheimer's disease: a possible mechanism of aluminium induced Alzheimer's

ABSTRACT

Alzheimer's disease attacks the brain causing gradual memory loss. Alzheimer's brain showed excess beta amyloid protein and neurofibrillary tangles, containing deposition of aluminium. Increasing evidence suggests that many neurons may die through apoptosis in Alzheimer's. Inducible nitric oxide synthase [iNOS] derived nitric oxide [NO] has been implicated in this process of neuronal cell death and apoptosis. Aluminium is considered a potential etiological factor in Alzheimer's disease and was used to produce an animal model of Alzheimer's. However, the exact mechanisms of aluminium induced Alzheimer's and neurotoxicity remain largely unknown. The present study was carried out to investigate the profile of the expression of iNOS in the hippocampus in an animal model of Alzheimer's produced by aluminium administration. Twenty four adult male albino rats were divided equally into four groups. Group I was the untreated control, groups II, III and IV were given aluminium chloride [300 mg/kg body weight] orally daily for one week, two and four weeks, respectively. At the end of the experiment, rats were killed by decapitation under brief anaesthesia. The brains were removed and processed for immunohistochemistry using antibody raised against iNOS. Results: By comparison to the untreated control, aluminium treated rats showed significant [P<0.05] increase in the expression of iNOS in the hippocampus. The expression was mainly neuronal and was seen in all areas. Additionally. administration of aluminium for four weeks caused marked histological changes with significant [P <0.05] reduction in hippocampus neuronal number and distortion of neuronal morphology. These data provide further evidence that exposure to aluminium may contribute to pathogenesis of Alzheimer 's and neurotoxicity by induction ofiNOS with subsequent increase in NO production that potentiate neuronal cell death in hippocampus